The ameliorating effects of low protein diets of high biologic value in the treatment of chronic kidney failure in human subjects are now well-documented. An explanation for the improvements observed with these dietary procedures might be that in uremia there are abnormalities in the metabolism of one or more amino acids that give rise to toxic symptoms. Decreasing the protein intake might result in decreased amino acid catabolism and consequent reduction in toxic metabolites. The amines constitute one class of metabolities that has been associated with uremic toxemia. However, the presumed toxic amino acid metabolites have not been explicitly identified and there are limitations to studies which can be performed with human subjects. It is therefore proposed to study amino acid metabolism in chronically uremic rats made azotemic by partial left renal artery ligation and contralateral nephrectomy. These animals exhibit altered plasma amino acid profiles similar to those observed in human renal failure and their survival rate is decreased when high protein diets are administered. It has now been shown that in these chronically uremic rats, there appear to be alterations in the metabolic pathways of a number of amino acids including phenylalanine, tryptophan and some urea cycle intermediates. These amino acids are all precursors of various amine compounds. Preliminary studies have already indicated that there are changes in brain serotonin metabolism in uremic rats. Hence, it is proposed to investigate further the metabolic pathways of these amino acids and amines particularly in relation to the toxic symptoms of uremia and uremic wasting. The effects of varying protein and amino acid intakes on these parameters will also be studied. If it can be established that only one or a few of the amino acids are primarily associated with the production of toxic symptoms in uremia, then the dietary management of human renal failure might be radically altered. BIBLIOGRAPHIC REFERENCES: Wang, M., Vyhmeister, I., Swendseid, M.E., and Kopple, J.D.: Phenylalanine hydroxylase and tyrosine aminotransferase activities in chronically uremic rats. J. Nutrit. 105:122-127, 1975. Wang, M., Vyhmeister, I., Kopple, J.D. and Swendseid, M.E: Effect of protein intake on weight gain and plasma amino acid levels in uremic rats. Am. J. Physiol. 230:1455-1459, 1976.